Granuloma Model Research Articles

A PHARMACOLOGICAL STUDY ON THE ANTI-INFLAMMATORY EFFECTS OF CALENDULA OFFICINALIS EXTRACT ON EXPERIMENTAL ANIMALS

Introduction: Calendula officinalis is one of those plants which have medicinal importance due to its flowers has pharmacological activity the important pharmacological parameters have been less investigated properly and can be scientifically proved by reverse pharmacology. It was found of interest to evaluate these properties of extract of flowers of Calendula officinalis scientifically in experimental models.
 Methods: Study was conducted in Albino Wistar rats.Fresh Calendula officinalis flowers were collected, extraction and drug formulation was made. Anti-inflammatory activity of hydroalcoholic extract of Calendula officinalis (HECO) flowers was studied in the Carrageenan induced paw edema model & Cotton pellet induced granuloma models The differences between experimental groups were compared by ANOVA followed by Students “t” unpaired test.
 Results: The Calendula officinalis extract of flowers at 200 and 400 mg/kg showed significant and highly significant inhibition (p< 0.05 and p<0.001, respectively) of paw edema after giving the carrageenan in the rat paw in comparison of control. In cotton pellets induced granuloma pouch method also, the Hydrochloric extract of Calendula officinalis (HECO) flowers showed very significant reduction of weight of granuloma (p<0.01) with 22.80% protection as compared with control.
 Conclusion: We conclude that the Anti-inflammatory activity was noted with Hydrochloric extract of Calendula officinalis in a dose-dependent manner in acute (carrageenan-induced hind paw edema model) as well as sub-acute (cotton pellet induced granuloma model) inflammatory experimental models. They decrease the chemical mediators of inflammation
 Key Words: Calendula Officinalis, anti inflammation, Paw Edema Model, granuloma pouch method , HECO

Mycobacterium tuberculosis extracellular vesicles induce the formation of granulomalike structures in an in vitro model

Abstract Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis. Only 10% of the infected individuals develop an active disease, while 90% of the infected individuals contain the mycobacteria inside structures known as granulomas, in a latent, asymptomatic state. The lung granuloma is formed by a core of infected macrophages, foam cells and epithelioid macrophages, surrounded by several lymphocyte subsets (CD4 T cells, CD8 T cells, Tγδ cells, NK cells, and B cells). M. tuberculosis releases extracellular vesicles, both spontaneously and under stress conditions; these vesicles carry components, derived from the mycobacterial cell wall, that are ligands for human Toll-like receptors (TLR) 2/6 and 4; as a result, these vesicles activate the innate immune system. To determine if M. tuberculosis extracellular vesicles induce the formation of a granuloma-like structure, we used an in vitro granuloma model, with peripheral blood mononuclear cells from individuals with latent TB (positive for the Quantiferon test). We found that M. tuberculosis extracellular vesicles induced the formation of granuloma-like structures that were similar in numbers, diameters and cellular composition (percentage of monocytes, T cells, Tγδ cells, NK cells and ILCs) to the granuloma-like structures formed in response to live M. tuberculosis H37Rv. These results suggest that M. tuberculosis extracellular vesicles participate in the cellular activation and migration processes that lead to granuloma formation in the lungs of TB patients. Supported by a grant 20190106 from Secretaría de Investigación y Posgrado, Instituto Politécnico Nacional.

In Vitro Granuloma Models of Tuberculosis: Potential and Challenges.

Despite intensive research efforts, several fundamental disease processes for tuberculosis (TB) remain poorly understood. A central enigma is that host immunity is necessary to control disease yet promotes transmission by causing lung immunopathology. Our inability to distinguish these processes makes it challenging to design rational novel interventions. Elucidating basic immune mechanisms likely requires both in vivo and in vitro analyses, since Mycobacterium tuberculosis is a highly specialized human pathogen. The classic immune response is the TB granuloma organized in three dimensions within extracellular matrix. Several groups are developing cell culture granuloma models. In January 2018, NIAID convened a workshop, entitled "3-D Human in vitro TB Granuloma Model" to advance the field. Here, we summarize the arguments for developing advanced TB cell culture models and critically review those currently available. We discuss how integrating complementary approaches, specifically organoids and mathematical modeling, can maximize progress, and conclude by discussing future challenges and opportunities.

ANTI-INFLAMMATORY ACTIVITY OF KNEMA ATTENUATA (HOOK. F. AND THOMSON) WARB ETHANOLIC STEM BARK EXTRACT IN ALBINO WISTAR RATS

Objective: Knema attenuata (Myristicaceae), popularly known as “wild nutmeg,” is an endemic tree species from Western Ghats, which has been used in folk medicine. Conventionally, the stem bark of K. attenuata is used for treating inflammatory conditions without any scientific information available for the same. The present study was undertaken to evaluate the anti-inflammatory activity of the ethanolic stem bark extract (ESBE) of K. attenuata using in vivo and in vitro screening models.
 Methods: The ethanolic extract of stem bark was prepared by soxhlation, and its cytotoxicity in RAW 264.7 cell line was assessed using MTT assay method. In vivo anti-inflammatory effect of extract was estimated in rats using carrageenan-induced paw edema model and cotton pellet-induced granuloma model. The in vitro anti-inflammatory activity of the extract was evaluated by cyclooxygenase and lipoxygenase inhibition assay, estimation of myeloperoxidase activity, and determination of cellular nitrite levels in lipopolysaccharide-stimulated RAW 264.7 macrophage cells.
 Results: Toxic symptoms were not observed for the ESBE. The extract demonstrated significant anti-inflammatory activity in both in vivo and in vitro models. The anti-inflammatory action exhibited by the extract was a result of the inhibition of leukocyte migration and nitric oxide pathway and partially by inhibition of mediators such as prostaglandins and leukotrienes.
 Conclusion: Findings from the study provide the evidence for the popular use of stem bark extract of K. attenuata as a potential anti-inflammatory agent.

Anti-Inflammation Effect of Small Molecule Oligopeptides Prepared from Panax ginseng C. A. Meyer in Rats.

The present study was designed to investigate the anti-inflammatory effects of ginseng oligopeptides (GOPs). For the anti-inflammatory activity, dextran-induced paw edema and granuloma models were used in Sprague-Dawley rats (180–200 g, 12 weeks old, n = 10). Rats were treated orally with GOPs (0, 62.5, 125, 250 and 500 mg/kg) for prophylaxis. In the granuloma model, the levels of NO, Tumor necrosis factor-α (TNF-α), interleukin IL-β, and interleukin IL-10 in serum were evaluated. In addition, in the edema model, the level of TNF-α, prostaglandin E2 (PGE2), Leukotriene D4 (LTD4), and the platelet activating factor (RAF) in paw tissue were detected. PCR assessed the effect of GOPs on the expression of MAPK and NF-κB. The results showed that oral administration of GOPs inhibited inflammation caused by cotton pellet and dextran. GOPs significantly inhibited the edema formation via MAPK and NF-κB. These findings suggested that GOPs have a beneficial effect on acute and chronic inflammation, and the mechanism possibly mediated by inhibiting gene expression involved in inflammation and downregulating inflammatory mediators.

Anti-inflammatory and analgesic activity based on polymorphism of cedrol in mice

Alternate forms of drug crystals display different physicochemical properties. These include stability, dissolution rate, bioavailability and solubility, which can affect pharmacokinetics and pharmacodynamics. It is therefore important to compare the crystal forms of cedrol to obtain optimal anti-inflammatory and analgesic effects. This study, for the first time, obtained and reports three novel forms (I-III) of cedrol polymorphs. The three forms of cedrol were recrystallized from seven organic solvents by slow cooling or volatilization and identified by thermal analysis, fourier transform infrared spectroscopy, scanning electron microscopy and powder X-ray diffraction analysis. Form I originated from acetone and cyclohexane. Form II was obtained from ethanol, ethyl acetate, acetonitrile and n-hexane. Form III was recrystallized from methanol. The anti-inflammatory and analgesic activities of the three crystalline forms were evaluated by acetic acid induced writhing in mice, the hot plate method, carrageenan induced mouse paw edema models, Xylene-induced mouse ear edema models and cotton pellet-induced mouse granuloma models. Experimental results revealed that the highest performance was achieved from Form I. These findings are of great significance during the early research study of cedrol polymorphs.

IL-13-regulated Macrophage Polarization during Granuloma Formation in an In Vitro Human Sarcoidosis Model.

The mechanisms underlying abnormal granuloma formation in patients with sarcoidosis are complex and remain poorly understood. A novel in vitro human granuloma model was used to determine the molecular mechanisms of granuloma genesis in patients with sarcoidosis in response to putative disease-causing mycobacterial antigens. Peripheral blood mononuclear cells (PBMCs) from patients with active sarcoidosis and from normal, disease-free control subjects were incubated for 7 days with purified protein derivative-coated polystyrene beads. Molecular responses, as reflected by differential expression of genes, extracellular cytokine patterns, and cell surface receptor expression, were analyzed. Unbiased systems biology approaches were used to identify signaling pathways engaged during granuloma formation. Model findings were compared with human lung and mediastinal lymph node gene expression profiles. Compared with identically treated PBMCs of control subjects (n = 5), purified protein derivative-treated sarcoidosis PBMCs (n = 6) were distinguished by the formation of cellular aggregates resembling granulomas. Ingenuity Pathway Analysis of differential expression gene patterns identified molecular pathways that are primarily regulated by IL-13, which promotes alternatively activated (M2) macrophage polarization. M2 polarization was further demonstrated by immunohistochemistry performed on the in vitro sarcoidosis granuloma-like structures. IL-13-regulated gene pathways were confirmed in human sarcoidosis lung and mediastinal lymph node tissues. The in vitro human sarcoidosis granuloma model provides novel insights into early granuloma formation, particularly IL-13 regulation of molecular networks that regulate M2 macrophage polarization. M2 macrophages are predisposed to aggregation and multinucleated giant cell formation, which are characteristic features of sarcoidosis granulomas. Clinical trial registered with www.clinicaltrials.gov (NCT01857401).

Existence and uniqueness of the solution to granuloma model in visceral leishmaniasi

In this paper we study a granuloma model in visceral leishmaniasis, which contains eleven coupled reaction diffusion equations. The existence and uniqueness of the model in the local solution is proved by using the Banach Fixed Point Theorem and theory of parabolic equation. Then, the existence and uniqueness of the global solution are obtained by using the extension method.

Exploration of anti-inflammatory and hepatoprotective effect of curcumin on co-administration with acetylsalicylic acid

Context: Acetylsalicylic acid (ASA) has been repositioned against different inflammatory disease conditions. However, on long-term use, ASA is reported to cause hepatotoxicity by compromising the antioxidant status. Curcumin is known for its antioxidant and anti-inflammatory action. Accordingly, co-use of curcumin can be expected to enhance the anti-inflammatory effects of ASA while minimizing its hepatotoxicity. Aims: To evaluate the anti-inflammatory and hepatoprotective effects of curcumin when co-administered with ASA. Methods: To evaluate anti-inflammatory activity carrageenan-induced paw edema and cotton pellet induced granuloma models were used. Hepatotoxicity was induced by administration of ASA (100 mg/kg/day) for 28 continuous days. Antioxidant effects were determined by malondialdehyde, superoxide dismutase and reduced glutathione assay of liver tissue. Results: Co-treatment with curcumin and ASA significantly (p<0.001) reduced (57.92%) the paw edema induced by carrageenan. The effect was higher than that of the ASA (45.51%) and curcumin (36.87%). Further, the combination showed higher (57.67%) inhibition of granuloma formation compared to that of ASA (34.22%) and curcumin (28.39%). Co-use of curcumin with ASA lowered the malondialdehyde level while relatively increasing the superoxide dismutase and reduced glutathione compared to ASA and curcumin. The histological findings showed protection against ASA induced hepatotoxicity. Conclusions: Curcumin showed additive effects with ASA against inflammatory granuloma formation in rats. It also showed positive interaction against carrageenan-induced inflammation. With relatively higher antioxidant capacity, the co-use of curcumin showed protection against ASA induced hepatotoxicity.

Evaluation of anti-inflammatory activity of ethanolic extract of Gmelina arborea in experimental acute and sub-acute inflammatory models in wistar rats

Background: Inflammation is a complex reaction to various injurious agents such as infections, trauma, foreign bodies, tissue necrosis, physical and chemical agents, that consists of vascular responses, migration and activation of leukocytes and systemic reactions. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are currently the most commonly prescribed drugs for treating pain and inflammation. The traditional NSAIDs usually cause various adverse effects on long term use. Gmelina arborea Linn (Gambhari) belongs to family Verbenaceae. The roots, leaves, flowers, fruits and bark are used for treating different ailments as anthelmintic, analgesic, anti-pyretic, antidiabetic, antimicrobial, diuretic and other common disorders.Methods: The study was carried out by using inflammatory models in wistar rats. The anti-inflammatory activity of G. arborea was compared with standard drug aspirin. The study parameters for acute inflammation was assessment of reduction in inflammation & the percentage inhibition of the paw edema. The parameter for the sub-acute inflammation was percentage inhibition of the dry granuloma weight.Results: The low and high dose of G. arborea root extract significantly showed the anti-inflammatory activity when compared to control group. The high dose of G. arborea extract showed comparable results in parameters like reducing inflammation, percentage inhibition of paw edema and dry granuloma weight in acute carrageenan paw edema and sub-acute inflammation cotton pellet granuloma models with standard aspirin treated group.Conclusions: Since G. arborea root extract was having all the qualities required for anti-inflammatory drug. However, no clear inference can be drawn at this stage and hence we consider the work for further extensive research.

A REVIEW ON IN VIVO AND IN VITRO EXPERIMENTAL MODELS TO INVESTIGATE THE ANTI-INFLAMMATORY ACTIVITY OF HERBAL EXTRACTS

The article emphasizes the anti-inflammatory effects of herbal extracts on different experimental models that are repeatedly used to test the in vivo anti-inflammatory activity of herbal components. Edema, granuloma and arthritis models are used to test the anti-inflammatory activity of plant extracts whereas formalin or acetic acid-induced writhing test and hot plate methods are the most repeatedly used to evaluate anti-nociceptive potentials of the herbal extracts. Although adjuvant-induced and collagen-induced arthritis models are also quite efficient, they have been used seldom to evaluate anti-inflammatory tendencies of the herbs. Here, we suggest a double positive reference model using both steroid and nonsteroidal anti-inflammatory drugs at the same time, instead of using only one of them either.

Human Monocytic Suppressive Cells Promote Replication of Mycobacterium tuberculosis and Alter Stability of in vitro Generated Granulomas.

Tuberculosis (TB) has tremendous public health relevance. It most frequently affects the lung and is characterized by the development of unique tissue lesions, termed granulomas. These lesions encompass various immune populations, with macrophages being most extensively investigated. Myeloid derived suppressor cells (MDSCs) have been recently identified in TB patients, both in the circulation and at the site of infection, however their interactions with Mycobacterium tuberculosis (Mtb) and their impact on granulomas remain undefined. We generated human monocytic MDSCs and observed that their suppressive capacities are retained upon Mtb infection. We employed an in vitro granuloma model, which mimics human TB lesions to some extent, with the aim of analyzing the roles of MDSCs within granulomas. MDSCs altered the structure of and affected bacterial containment within granuloma-like structures. These effects were partly controlled through highly abundant secreted IL-10. Compared to macrophages, MDSCs activated primarily the NF-κB and MAPK pathways and the latter largely contributed to the release of IL-10 and replication of bacteria within in vitro generated granulomas. Moreover, MDSCs upregulated PD-L1 and suppressed proliferation of lymphocytes, albeit with negligible effects on Mtb replication. Further comprehensive characterization of MDSCs in TB will contribute to a better understanding of disease pathogenesis and facilitate the design of novel immune-based interventions for this deadly infection.

PPARγ is critical for Mycobacterium tuberculosis induction of Mcl-1 and limitation of human macrophage apoptosis.

Peroxisome proliferator-activated receptor (PPAR)γ is a global transcriptional regulator associated with anti-inflammatory actions. It is highly expressed in alveolar macrophages (AMs), which are unable to clear the intracellular pathogen Mycobacterium tuberculosis (M.tb). Although M.tb infection induces PPARγ in human macrophages, which contributes to M.tb growth, the mechanisms underlying this are largely unknown. We undertook NanoString gene expression analysis to identify novel PPARγ effectors that condition macrophages to be more susceptible to M.tb infection. This revealed several genes that are differentially regulated in response to PPARγ silencing during M.tb infection, including the Bcl-2 family members Bax (pro-apoptotic) and Mcl-1 (pro-survival). Apoptosis is an important defense mechanism that prevents the growth of intracellular microbes, including M.tb, but is limited by virulent M.tb. This suggested that M.tb differentially regulates Mcl-1 and Bax expression through PPARγ to limit apoptosis. In support of this, gene and protein expression analysis revealed that Mcl-1 expression is driven by PPARγ during M.tb infection in human macrophages. Further, 15-lipoxygenase (15-LOX) is critical for PPARγ activity and Mcl-1 expression. We also determined that PPARγ and 15-LOX regulate macrophage apoptosis during M.tb infection, and that pre-clinical therapeutics that inhibit Mcl-1 activity significantly limit M.tb intracellular growth in both human macrophages and an in vitro TB granuloma model. In conclusion, identification of the novel PPARγ effector Mcl-1 has determined PPARγ and 15-LOX are critical regulators of apoptosis during M.tb infection and new potential targets for host-directed therapy for M.tb.

Steroidal alkaloid solanine A from Solanum nigrum Linn. exhibits anti-inflammatory activity in lipopolysaccharide/interferon γ-activated murine macrophages and animal models of inflammation

Solanine A is a novel steroidal alkaloid isolated from Solanum nigrum Linn., a medicinal and edible plant which is widely used for treating various inflammatory diseases. In this study, we found that solanine A markedly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide/interferon-γ (LPS/IFNγ)-stimulated RAW264.7 cells, and attenuated xylene, carrageenan and agar-induced inflammation in mice. The mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1β (IL-1β), as well as C-X-C motif chemokine ligand-9 (CXCL9), were significantly decreased by solanine A. Furthermore, solanine A also suppressed LPS/IFNγ-induced protein expression of iNOS and COX2. Mechanistically, solanine A inhibited the nuclear translocation of nuclear factor-κB (NF-κB) through the prevention of NF-κB p65 and inhibitory κB-α (IκBα) phosphorylation and IκBα degradation, and it also suppressed activation of extracellular regulated protein kinases (ERK), signal transducers and activators of transcription-1 (STAT1) and serine/threonine protein kinase Akt in LPS/IFNγ-stimulated RAW264.7 macrophages and agar-induced granuloma model in mice. Taken together, solanine A exhibits a potent anti-inflammatory activity in LPS/IFNγ- activated macrophages and animal models of inflammation through inhibition of NF-κB, ERK1/2, Akt and STAT1 signaling pathways, suggesting that solanine A may be a valuable leading compound in the treatment of inflammatory diseases.

ANTI-INFLAMMATORY AND ANTI-GRANULOMA ACTIVITY OF SULFORAPHANE, A NATURALLY OCCURRING ISOTHIOCYANATE FROM BROCCOLI (BRASSICA OLERACEA)

Objective: The objective of this study was to establish the anti-inflammatory activity of sulforaphane (SFN) in different acute and subchronic models of inflammation. Methods: The anti-inflammatory activity of SFN was evaluated by the secretion of proinflammatory cytokines in rat peripheral blood mononuclear cells (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-α]) which are important mediators of inflammation as determined by enzyme-linked immunosorbent assay. Furthermore, paw volume was determined in various acute models of inflammation, and percentage inhibition of granuloma tissue was assessed by cotton pellet-induced granuloma model. From serum, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase levels were determined which is followed by assay for estimation of antioxidants such as superoxide dismutase (SOD), catalase, and glutathione (GSH). Results: SFN showed significant anti-inflammatory activity against paw edema induced by carrageenin/histamine/egg-albumin. A remarkable control in inflammation was observed most notably at the highest test dose of 5 mg/kg in the subchronic granuloma model. In addition, the release of inflammatory cytokines such as IL-6 and TNF-α which is responsible for inflammatory activity gets attenuated by SFN (∗p<0.05; ∗∗p< 0.01). Moreover, toxic control rats showed significant decreased levels of GSH, catalase, and SOD and increased the level of serum hepatic enzymes which gets reversed by SFN in dose-dependent manner. Conclusions: The present findings demonstrated that SFN can recover inflammation by inhibiting TNF-α and IL-6 in inflammation process.

Functionalized spirooxindole-indolizine hybrids: Stereoselective green synthesis and evaluation of anti-inflammatory effect involving TNF-α and nitrite inhibition

Stereoselective synthesis of a small library of novel spiroheterocyclic hybrids including indolizine, oxindole, and substituted piperidine units has been accomplished in [bmim]Br using a [3 + 2] cycloaddition strategy in good yield and were tested for their anti-inflammatory activities. The effects of compounds (4a-o) against inflammation were studied using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, and cotton pellet-induced granuloma models. Among the heterocyclic hybrids, compounds 4d, 4g, and 4o showed significant anti-inflammatory activities against acute and chronic inflammatory models. These compounds also showed significant inhibition of PGE2, TNF-α, and nitrite levels in carrageenan-induced hind paw oedema. Thus it is evident from our study that these novel spiroheterocyclic hybrids 4d, 4g, and 4o displayed significant anti-inflammatory effects that involve the reduction of PGE2, TNF-α, and nitrite levels.

Use of a leukocyte-targeted peptide probe as a potential tracer for imaging the tuberculosis granuloma

Granulomas are the histopathologic hallmark of tuberculosis (TB), both in latency and active disease. Diagnostic and therapeutic strategies that specifically target granulomas have not been developed. Our objective is to develop a probe for imaging relevant immune cell populations infiltrating the granuloma. We report the binding specificity of Cyanine 3 (Cy3)-labeled cFLFLFK-PEG12 to human leukocytes and cellular constituents within a human in vitro granuloma model. We also report use of the probe in in vivo studies using a mouse model of lung granulomatous inflammation. We found that the probe preferentially binds human neutrophils and macrophages in human granuloma structures. Inhibition studies showed that peptide binding to human neutrophils is mediated by the receptor formyl peptide receptor 1 (FPR1). Imaging the distribution of intravenously administered cFLFLFK-PEG12-Cy3 in the mouse model revealed probe accumulation within granulomatous inflammatory responses in the lung. Further characterization revealed that the probe preferentially associated with neutrophils and cells of the monocyte/macrophage lineage. As there is no current clinical diagnostic imaging tool that specifically targets granulomas, the use of this probe in the context of latent and active TB may provide a unique advantage over current clinical imaging probes. We anticipate that utilizing a FPR1-targeted radiopharmaceutical analog of cFLFLFK in preclinical imaging studies may greatly contribute to our understanding of granuloma influx patterns and the biological roles and consequences of FPR1-expressing cells in contributing to disease pathogenesis.

Anti-inflammatory Effect of an Extract of Agave americana on Experimental Animals.

Background:Medicinal plants have the potential treasure to treat medical conditions for a long time based on error and trial method. Agave americana has been known as century plant or American aloe. The leaves contain genins, saponins, steroidal flavonoids, isoflavones, and coumarins. It has long been used for anti-inflammatory effects.Objectives:This study was designed to evaluate the anti-inflammatory activity of the extract of A. americana.Materials and Methods:A. americana leaves extract is collected and the extract is done by percolation method. Inflammation is induced in experimental animals' carrageenan-induced paw edema model and cotton pellet-induced granuloma model. The extract of A. americana and standard, aspirin and indomethacin are given orally for the anti-inflammatory effects. The anti-inflammatory effects were measured at regular intervals of time to see the percentage inhibition of paw edema and reduction of weight of granuloma with percentage protection to compare the effect of the extract with the control and standard.Results:The extract of A. americana showed improved in percentage inhibition of paw edema in graded doses of hydroalcoholic extract of A. americana (HEAA) as compared with control in carrageenan-induced paw edema model. The percentage inhibition of 400 mg/kg of HEAA at the 3rd h is almost comparable with the standard, aspirin. On the other hand, graded doses (200 and 400 mg/kg) showed a highly significant reduction (P < 0.001) in the weights of granuloma in comparison with the control in cotton pellet-induced granuloma model. The percentage inhibition of weight of granuloma by 400 mg/kg of HEAA is quite comparable to the standard, Indomethacin.Conclusion:Anti-inflammatory activity is seen with the graded dose of HEAA. The plant contains flavonoids and genins which have been shown to have anti-edematous effects in the acute phase of inflammation. Thus, the plant contributes to its anti-inflammatory activity. Thus, higher doses of A. americana leaves need to be used to have the better understanding of the mechanism of anti-inflammation.SUMMARY The hydroalcoholic extract from Agave americana (100, 200, and 400 mg/kg, HEAA) were studied in carrageenan-induced paw edema model and cotton pellet-induced granuloma model in Wistar rats. The plant contains flavonoids and genins which have been shown to have anti-edematous effects in the acute phase of inflammation. The results were good with the higher doses of 200 and 400 mg/kg of HEAA. Its in vivo anti-inflammatory activity is in good agreement with the traditional use of A. americana. Abbreviation Used: HEAA: Hydroalcoholic extract of Agave americana leaves; SEM: Standard error mean; ANOVA: Analysis of variance; n: Number; g: gram; w/w: weight by weight; h: hour; kg: kilogram; mg: milligram

To evaluate the anti-inflammatory activity of ramipril in albino rats

Background: Angiotensin II (Ang II) is a product of Renin angiotensin aldosterone system (RAAS). Angiotensin‑II regulates vascular tone, stimulates the release of pro‑inflammatory cytokines, activates nuclear factor‑kappa B (NF‑κB), increases oxidant stress and functions as an inflammatory molecule. Ramipril an ACE inhibitor act by inhibiting angiotensin converting enzyme, decreases angiotensinogen II activity. Hence the present was to evaluate the anti-inflammatory activity of Ramipril.Methods: Eighteen Wistar albino rats weighing around 150-200gms of either sex were randomly selected from central animal facility and divided into three groups. The control group received normal saline 25ml/kg, standard group received Indomethacin 10mg/kg and test group received Ramipril (0.9mg/kg) orally for six days. The animals were subjected to carrageenan induced paw oedema and cotton pellet induced granuloma model.Results: Ramipril significantly decreased the mean paw oedema in carrageenan induced paw oedema when compared to control and in cotton pellet induced granuloma Ramipril decreased the mean granuloma weight when compared to control.Conclusions: Ramipril showed anti-inflammatory activity when given for 6 consecutive days per orally in albino rats in carrageenan induced paw oedema and cotton pellet induced granuloma model.

Deletion of TGF-β1 Increases Bacterial Clearance by Cytotoxic T Cells in a Tuberculosis Granuloma Model.

Mycobacterium tuberculosis is the pathogenic bacterium that causes tuberculosis (TB), one of the most lethal infectious diseases in the world. The only vaccine against TB is minimally protective, and multi-drug resistant TB necessitates new therapeutics to treat infection. Developing new therapies requires a better understanding of the complex host immune response to infection, including dissecting the processes leading to formation of granulomas, the dense cellular lesions associated with TB. In this work, we pair experimental and computational modeling studies to explore cytokine regulation in the context of TB. We use our next-generation hybrid multi-scale model of granuloma formation (GranSim) to capture molecular, cellular, and tissue scale dynamics of granuloma formation. We identify TGF-β1 as a major inhibitor of cytotoxic T-cell effector function in granulomas. Deletion of TGF-β1 from the system results in improved bacterial clearance and lesion sterilization. We also identify a novel dichotomous regulation of cytotoxic T cells and macrophages by TGF-β1 and IL-10, respectively. These findings suggest that increasing cytotoxic T-cell effector functions may increase bacterial clearance in granulomas and highlight potential new therapeutic targets for treating TB.